Action potential-driven current transients were recorded from sensory cilia and used to monitor the spike frequency generated by olfactory receptor neurons, which were maintained in their natural position in the sensory epithelium. Both basal and messenger-induced activities, as elicited with forskolin or cyclic nucleotides, were dependent on the presence of mucosal Na +. The spike rate decreased to ~ 20% when mucosal Na ÷ was lowered from 120 to 60 mM (replaced by N-methyl-D-glucamine+), without clear changes in amplitude and duration of the recorded action potential-driven transients. Mucosal Ca 2÷ and Mg ~+ blocked spike discharge completely when increased from 1 to 10 mM in Ringer solution. Lowering mucosal Ca ~+ below 1 mM increased the spike rate. These results can be explained by the presence of a cyclic nucleotide-dependent, Ca~+-sensitive cation conductance, which allows a depolarizing Na ÷ inward current to flow through the apical membrane of in situ receptor cells. A conductance with these properties, thought to provide the receptor current, was first described for isolated olfactory cells by Nakamura and Gold (1987. Nature (Lond.). 325:442--444). The forskolin-stimulated spike rate decreased when/-c/s-diltiazem, a known blocker of the cyclic nucleotidedependent receptor current, was added to the mucosal solution. Spike rate also decreased when the mucosal K ÷ concentration was lowered. Mucosal Ba ~÷ and 4-aminopyridine, presumably by means of cell depolarization, rapidly increased the spike rate. This suggests the presence of apical K ÷ channels that render the receptor cells sensitive to the K + concentration of the olfactory mucus. With a slower time course, mucosal Ba 2+ and 4-aminopyridine decreased the amplitude and caused rectification of the fast current transients (prolongation of action potentials). Abolishment of the apical Na ÷ current (by removal of mucosal Na+), as indicated by a strong decrease in spike rate, could be counteracted by adding 10 mMBa 2÷ or 1 mM 4-aminopyridine to the mucosal solution, which re-established spiking. Similarly, blockage of the apical cation conductance with 10 mM Ca could be counteracted by adding 10 mMBa 2+ or by raising the mucosal K ÷ concentration. Thus Address reprint requests to Dr. B. Lindemann,